Wnt-responsive element controls Lef-1 promoter expression during submucosal gland morphogenesis

Area of Science:

• Developmental Biology
• Gene Regulation
• Epithelial Biology

Background:

• Lymphoid enhancer factor 1 (Lef-1) is crucial for epithelial bud formation in airway submucosal glands and mammary glands.
• The specific regulatory regions of the Lef-1 promoter controlling this development are not fully understood.
• Wnt signaling pathways are known to influence Lef-1 expression.

Purpose of the Study:

• To investigate the role of a Wnt-responsive element (WRE) in the Lef-1 promoter during airway and mammary gland development.
• To define the spatial and temporal regulatory regions of the Lef-1 promoter in vivo.
• To assess the impact of Wnt-1 and Wnt-3a/beta-catenin signaling on Lef-1 promoter activity.

Main Methods:

• Utilized LacZ reporter transgenic mice to analyze Lef-1 promoter activity in vivo.
• Constructed Lef-1 promoter fragments, including one with the WRE deleted.
• Examined promoter activity in airway and mammary epithelial cell lines.
• Evaluated reporter gene expression patterns during glandular bud formation.

Main Results:

• A 2.5-kb Lef-1 promoter fragment partially recapitulated endogenous Lef-1 expression in both mammary and airway submucosal gland development.
• Deletion of the 110-bp WRE abolished Lef-1 promoter activity in nasal and tracheal submucosal glandular buds.
• Removal of the WRE did not significantly affect Lef-1 developmental expression in mammary glandular buds.
• The Lef-1 promoter demonstrated responsiveness to Wnt-1 signaling in both airway and mammary epithelial cells.

Conclusions:

• Wnt regulation of the Lef-1 promoter via the WRE is critical for airway submucosal glandular bud formation.
• The WRE's role in Lef-1 regulation differs between airway submucosal and mammary gland development.
• These findings highlight a specific mechanism of Lef-1 transcriptional control in airway development.